Neoplasms

All Conditions

Diseases and Abnormalities at or Before Birth

Skin and Connective Tissue Diseases

Hemangioma

Hemangioma, Capillary

Port-Wine Stain

Neoplasms, Vascular Tissue

Neoplasms by Histologic Type

Congenital Abnormalities

Skin Abnormalities

Skin Diseases

Pharmaceutical Solutions

All Drugs and Chemicals

Anti-Arrhythmia Agents

Antihypertensive Agents

Timolol

Maleic acid

Enzyme Inhibitors

Adrenergic beta-Antagonists

Adrenergic Agents

Adrenergic Antagonists

Neurotransmitter Agents

Subjects assigned to this arm will be randomized to 0.25% timolol for 180 days. If during the 180 days the subject is considered a treatment failure, the subject will be unblinded. If the subject is on 0.25% timolol they will be changed to 0.5% timolol.

Subjects assigned to this arm will be randomized to 0.5% timolol for 180 days. If during the 180 days the subject is considered a treatment failure, the subject will be unblinded. If the subject is on 0.5% timolol the treating physician will decide to either continue 0.5% timolol or withdraw the subject and begin an alternative treatment.

Subjects assigned to this group will not receive treatment. The subject will only be photographed on the same schedule as the intervention group.

50:50 Randomized 0.25% Timolol Maleate Gel Forming Solution

0.25% Timolol Maleate Gel Forming Solution

50:50 Randomized 0.5% Timolol Maleate Gel Forming Solution

0.5% Timolol Maleate Gel Forming Solution

Kanecia Zimmerman, MD, MHS

Kristin Holland, MD

The purpose of this study is to assess the safety and efficacy of Timolol 0.25% and 0.5% doses.

Primary: Describe the efficacy of 0.25% and 0.5% topical timolol maleate Gel-forming solution (GFS) as assessed through Infantile Hemangioma (IH) changes in volume.

Secondary: Describe the safety of topical timolol maleate GFS for treatment of IH.

Efficacy, Safety and Pharmacokinetics of Topical Timolol in Infants With Infantile Hemangioma (IH)

Efficacy, Safety, and Pharmacokinetics of Timolol in Infants With Infantile Hemangioma (IH)

The PK blood samples will be 1.0 ml each and collected between the following timeframes after application of Timolol: within 2 hours, 2-4 hours, 5-7 hours, 8-10 hours or 11-12 hours.

The VAS-volume is a 100 mm scale used to independently grade hemangioma volume. -100 indicates hemangioma has doubled in size, 0 indicates no change, and +100 indicates complete shrinkage. Partial response is defined as \>20% and up to 80% reduction in volumetric size of hemangioma.

The VAS-color is a 100 mm scale used to independently grade hemangioma color. -100 indicates hemangioma is twice as intense, 0 indicates no change, and +100 indicates complete resolution. Partial response is defined as \>30% and up to 80% reduction in color of hemangioma.

Comparison of partial response of hemangioma color (partial response or greater as assessed by VAS-color) between the two treatment arms. Partial response: \>30% and up to 80% reduction in color of hemangioma.

Absolute change in hemangioma dynamic complication scale from Day 0 to end of study within each treatment arm. The HDCS provides a 6-point severity grading system for 12 individual hemangioma-related complications (grade 0 represents absent to minimal; grade 5 = most severe). The total score ranges from 0-60.

Assess time to partial response or greater by VAS-volume, comparing baseline to day 30, day 60, day 120 and day 180. Partial response: \>20% and up to 80% reduction in volumetric size of hemangioma

Assess time to partial response or greater by VAS-color, comparing baseline to day 30, day 60, day 120 and day 180. Partial response: \>30% and up to 80% reduction in color of hemangioma

Absolute change in IH-QoL score scale from Day 0 to end of study within each treatment arm. The IH-QoL score scale consists of 4 domains (physical symptom of patient, social functioning of patient, social and psychological functioning of caregiver, and emotional functioning of caregiver) and 29 items, with each item scored on a Likert scale : 0 = never a problem, 1 = almost never a problem, 2 = sometimes a problem, 3 = often a problem and 4 = almost always a problem). The total range is 0-116; the higher the total number indicates a worse outcome.

Serious adverse events and adverse events of special interest from randomization to Day 180 in infants treated with topical timolol maleate (0.25% and 0.5%) GFS for the treatment of infantile hemangioma.

The Emmes Company, LLC

National Institutes of Health (NIH)

Kanecia Obie Zimmerman

Principal Investigator

0 participants in the historical control arm were at risk for Adverse Events because they did not prospectively participate in this research study. Only data that had already been collected was used in this study.

Subjects assigned to this arm will be randomized to 0.25% timolol for 180 days. If during the 180 days the subject is considered a treatment failure, the subject will be unblinded. If the subject is on 0.25% timolol they will be changed to 0.5% timolol.

0.25% Timolol Maleate Gel Forming Solution: 50:50 Randomized 0.25% Timolol Maleate Gel Forming Solution

0.25% Timolol Treatment

Subjects assigned to this arm will be randomized to 0.5% timolol for 180 days. If during the 180 days the subject is considered a treatment failure, the subject will be unblinded. If the subject is on 0.5% timolol the treating physician will decide to either continue 0.5% timolol or withdraw the subject and begin an alternative treatment.

0.5% Timolol Maleate Gel Forming Solution: 50:50 Randomized 0.5% Timolol Maleate Gel Forming Solution

0.5% Timolol Treatment

Non-Intervention Group

To obtain sufficient age-matched controls, data and clinical photographs collected as part of a similar study (EudraCT 2013-005199-17) were included in the analysis of certain outcome measures as noted in the Analysis Population Description of those measures.

Historical Controls

Historical Control Group

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Kanecia Zimmerman, MD, PhD, MPH

The Historical Control group was included with the Non-intervention group. Excludes 8 participants (four in the 0.5% dosage and four in the historical placebo controls) with out come determined to be unevaluable as they have no reported VAS scores

Number of Participants With Partial Response of Hemangioma Volume as Measured by VAS (Visual Analog Scale) Within Each Treatment Arm and Compared With Untreated Controls

The Historical Control group was included with the Non-intervention group. Only participants with evaluable data were included in the analysis.

Number of Participants With Partial Response in Hemangioma Color as Measured by VAS (Visual Analog Scale) Within Each Treatment Arm and Compared With Untreated Controls

Only participants with evaluable data were included in the analysis.

Number of Participants With Partial Response of Hemangioma Volume as Measured by VAS (Visual Analog Scale) Within Each Treatment Arm

Comparison of Partial Response of Hemangioma Color From Baseline to 180 Days, Within Each Treatment Arm

Change in Hemangioma Dynamic Complication Scale (HDCS)

30-Day Visit

60-Day Visit

120-Day Visit

180-Day Visit

Number of Participants Who Reach Partial Response, Assessed by Volume

Number of Participants Who Reach Partial Response, Assessed by Hemangioma Color

Change in Hemangioma Quality of Life (IH-QoL) Assessment for Infants

AEs of Special Interest

Serious AEs

Only participants who received treatment and had evaluable data were included in this analysis

Spots Global Cancer Trial Database for Efficacy, Safety and Pharmacokinetics of Topical Timolol in Infants With Infantile Hemangioma (IH)

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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